Association of vitamin D receptor and 17 hydroxylase gene polymorphisms with benign prostatic hyperplasia and benign prostatic enlargement

Urology. 2001 Mar;57(3):567-72. doi: 10.1016/s0090-4295(00)01004-9.

Abstract

Objectives: To determine whether polymorphisms in 17 hydroxylase (CYP17) and vitamin D receptor (VDR) genes have an association to prostate volume/histology and endocrine patterns in elderly men with lower urinary tract symptoms (LUTS).

Methods: Elderly men with LUTS underwent the following investigations: International Prostate Symptom Score (IPSS), uroflowmetry, serum prostate-specific antigen (PSA) assessment of prostate volume, and an endocrine study. Polymorphisms of CYP17 (T-->C substitution in the 5' promoter region) and VDR (T1055C) genes were detected by polymerase chain reaction followed by restriction-length polymorphism analysis, using DNA from peripheral white blood cells. Clinical and endocrine parameters and the prostate stroma/epithelial ratio were correlated to CYP17 and VDR genotypes.

Results: A total of 148 (mean +/- SD, 67.0 +/- 9.7 years) patients were analyzed. IPSS (17.8 +/- 7.0), prostate volume (41.9 +/- 17.9 cc), maximum flow rate (10.9 +/- 5.8 mL/s), and PSA (4.7 +/- 4.7 ng/mL) indicate a typical LUTS population. Mean endocrine levels were consistently within age-specific reference values. Neither CYP17 nor VDR gene polymorphisms revealed an association to prostate size, PSA, clinical parameters, and endocrine parameters. Men who had the A1/A1 CYP17 genotype had on average a greater stromal/epithelial ratio than men with the A1/A2 or A2/A2 genotypes, yet after adjusting for multiple testing, this significance disappeared.

Conclusions: Gene polymorphisms of CYP17 and VDR have no association to prostate volume, clinical parameters, and endocrine parameters in elderly men. The association of CYP17 polymorphism and prostate histology warrants further studies. Assessment of gene polymorphisms might provide new insights into the pathogenesis of benign prostatic hyperplasia and benign prostate enlargement and may hold promise as genetic biomarkers of this disease.

MeSH terms

  • Aged
  • Biopsy
  • Case-Control Studies
  • Dehydroepiandrosterone / blood
  • Estradiol / blood
  • Follicle Stimulating Hormone / blood
  • Humans
  • Hypertrophy / blood
  • Hypertrophy / enzymology
  • Hypertrophy / pathology
  • Luteinizing Hormone / blood
  • Male
  • Polymorphism, Genetic
  • Prostate / pathology
  • Prostate-Specific Antigen / blood
  • Prostatic Hyperplasia / blood
  • Prostatic Hyperplasia / enzymology
  • Prostatic Hyperplasia / pathology*
  • Receptors, Calcitriol / genetics*
  • Steroid 17-alpha-Hydroxylase / biosynthesis
  • Steroid Hydroxylases / genetics*
  • Testosterone / blood

Substances

  • Receptors, Calcitriol
  • Testosterone
  • Dehydroepiandrosterone
  • Estradiol
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Steroid Hydroxylases
  • Steroid 17-alpha-Hydroxylase
  • Prostate-Specific Antigen